Genetics and Genomics Commons^™

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

All ETDs from UAB

The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

All ETDs from UAB

Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …

Plural Molecular And Cellular Mechanisms Of Pore Domain, Timothy J Abreo, Emma C Thompson, Anuraag Madabushi, Kristen L Park, Heun Soh, Nissi Varghese, Carlos G Vanoye, Kristen Springer, Jim Johnson, Scotty Sims, Zhigang Ji, Ana G Chavez, Miranda J Jankovic, Bereket Habte, Aamir R Zuberi, Cathleen M Lutz, Zhao Wang, Vaishnav Krishnan, Lisa Dudler, Stephanie Einsele-Scholz, Jeffrey L Noebels, Alfred L George, Atul Maheshwari, Anastasios Tzingounis, Edward C Cooper

Faculty, Staff and Students Publications

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. Kcnq2G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal …

Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee

Faculty, Staff and Students Publications

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture …

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …

Measuring Spatial And Temporal Variation In Species Composition Of Ephemeral Pond Amphibian Assemblages Using Metabarcoding, Elizabeth Strasko

Masters Theses & Specialist Projects

Amphibian populations worldwide face severe threats, heightening the need for reliable monitoring methods. In this thesis, I explored and tested environmental DNA (eDNA) metabarcoding protocols to survey amphibian assemblages in ephemeral ponds of the the Green River Preserve in central Kentucky, USA. First, I evaluated whether the commonly used mitochondrial cytochrome c oxidase subunit I (COI) gene could effectively capture species-level variation in local amphibians for eDNA metabarcoding. Extensive primer design and testing revealed significant challenges in amplifying fragmented eDNA from water samples. In a second study, I applied a metabarcoding approach using the mitochondrial 12S ribosomal RNA (12S) gene …

The Cdk8 Kinase Module: A Novel Player In The Transcription Of Translation Initiation And Ribosomal Genes, Brittany Friedson, Stephen D Willis, Natalia Shcherbik, Alicia N Campbell, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Survival following stress is dependent upon reprogramming transcription and translation. Communication between these programs following stress is critical for adaptation but is not clearly understood. The Cdk8 kinase module (CKM) of the Mediator complex modulates the transcriptional response to various stresses. Its involvement in regulating translational machinery has yet to be elucidated, highlighting an existing gap in knowledge. Here, we report that the CKM positively regulates a subset of ribosomal protein (RP) and translation initiation factor (TIF)-encoding genes under physiological conditions in Saccharomyces cerevisiae. In mouse embryonic fibroblasts and HCT116 cells, the CKM regulates unique sets of RP and TIF …

Determining Localization Of Surf-4 In Drosophila Melanogaster In The Secretory Pathway, Jada Scott

Mahurin Honors College Capstone Experience/Thesis Projects

The purpose of this research is to determine the role of the Surfeit-4 gene, or Surf-4 locus protein, during Drosophila melanogaster development. Surf-4 was identified in the Srivastava lab in a biochemical screen for proteins that associate with the basement membrane (BM): a structure needed and required for normal development and its degradation is a hallmark of tumor metastasis. Surf-4 has been predicted to function within intracellular compartments and is known to be expressed in many parts of the developing fly. We are currently determining why Surf-4 is important in development and what role, if any, it could play during …

Graduate Student Literature Review From "The Development Of The Brouwer Equation To Estimate Heat Production: Past, Present, And Future Perspectives" In Journal Of Dairy Science (2025), Addison L. Carroll, Paul J. Kononoff, Tami M. Brown-Brandl

Department of Animal Science: Faculty Publications

Appendix 1, supplemental to "The development of the Brouwer equation to estimate heat production: Past, present, and future perspectives," Journal of Dairy Science (2025).

Noncoding Rnas In Nuclear Organization, Thembalami Dube , '24, Dawn M. Carone

Biology Faculty Works

No abstract provided.

Covariate Selection For Rna-Seq Differential Expression Analysis With Hidden Factor Adjustment, Farzana Noorzahan, Hyeongseon Jeon, Yet Nguyen

Mathematics & Statistics Faculty Publications

In RNA-seq data analysis, a primary objective is the identification of differentially expressed genes, which are genes that exhibit varying expression levels across different conditions of interest. It is widely known that hidden factors, such as batch effects, can substantially influence the differential expression analysis. Furthermore, apart from the primary factor of interest and unforeseen artifacts, an RNA-seq experiment typically contains multiple measured covariates, some of which may significantly affect gene expression levels, while others may not. Existing methods either address the covariate selection or the unknown artifacts separately. In this study, we investigate two integrated strategies, FSR_sva and SVAall_FSR, …

Clonal Variation In Effector Gene Expression As A Mechanism For Pathogenic Adaptation In Magnaporthe Oryzae, Rebekah J. Ellsworth

Theses and Dissertations--Plant Pathology

Magnaporthe oryzae is a filamentous fungal pathogen that causes destructive diseases in cereals, including rice blast, wheat blast, and gray leaf spot. It is responsible for 10–30% annual yield losses in rice (Nalley et al., 2016) and up to 100% loss in wheat under favorable conditions (Kohli et al., 2011). Disease management typically relies on the use of resistant cultivars, but M. oryzae rapidly overcomes host resistance by mutating or deleting avirulence (AVR) genes recognized by host immune receptors. This rapid adaptation, often occurring within one to two growing seasons, presents a major challenge to breeding for durable resistance.

The …

Feasibility Of Producing Non-Structural Wood Products Using Trembling Aspen Lumber, Mengyuan Zhang

Aspen Bibliography

Trembling aspen (Populus tremuloides) is abundant in Canada but underutilized in non-structural solid wood products.This study was aimed at evaluating the feasibility of using aspen lumber to produce flooring, moulding, and siding. The shrinkage, surface roughness, and wettability of aspen wood were tested. The surface hardness, screw withdrawal resistance, colour change, and dimensional stability of there products fabricated were examined. The wood yield of each product was analyzed. It was found that aspen showed superior machinability and wettability to silver maple and yellow poplar. Aspen flooring had a Brinell hardness of 13.47 MPa, 60% lower than silver maple. …

Microsatellites Reveal The Population Genetic Structure Of Yellow Perch In Minnesota, Megan Boche

Journal of Earth and Life Science

When analyzing a population’s genetic makeup, looking at variation of individuals and populations is a crucial factor. The management of yellow perch will be aided by this information particularly in regard to stocking or relocation. Microsatellite loci were used to analyze the genetic population structure of yellow perch Perca flavescens within and among 29 sampling areas throughout Minnesota’s basins. Seven microsatellite DNA loci were evaluated, with heterozygosities ranging from 0.41 to 0.78. The Lower Mississippi basin samples showed higher numbers of alleles per locus and greater expected heterozygosities compared to other basins, with Lake Pepin (PEP) exhibiting the highest average …

Marine Heatwave Response Plan For Western Australia’S Wild Capture Fisheries And Aquaculture, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

The purpose of the Western Australian wild capture fisheries and aquaculture marine heatwave response plan (the Plan) is to document the Department’s approach for identifying and responding to the hazard of a marine heatwave on wild catch fisheries (commercial, recreational, charter and customary) and aquaculture resources within the geographic boundaries of WA. It provides risk reduction strategies and establishes best-practice processes for each stage of the hazard management and response continuum, ensuring that DPIRD is able to adequately prepare for, respond to, and recover from marine heatwave events. This Plan operates in conjunction with WA’s existing aquatic resource management framework, …

Snake Venoms As Models For Understanding The Origins And Evolution Of Gene Regulatory Networks, Siddharth S. Gopalan

Biology Dissertations - Archive

Understanding the relationship between genotype and phenotype is a fundamental goal of biology. However, the vastly complex nature of eukaryotic gene regulation can make deriving precise relationships between genotype and phenotype challenging. The gene regulatory architecture of snake venom systems provide an opportunity to study this problem in a phenotypic system with immense variation in phenotypes and the underlying genetics. Using a set of integrated functional genomic approaches with snake venoms as a central model, in this dissertation, I provide several examples of the regulatory mechanisms by which diversity in phenotypes arises. Specifically, I identify how gene expression heterogeneity between …

Genetic Analysis Of Methionine Restriction-Associated Mitochondrial Unfolded Protein Response Signaling., Josh D. Dodge

Biology Dissertations - Archive

The lifespan of an organism is dictated by various genetic and environmental factors. One such determinant is the health of mitochondria which are organelles that mediate various critical cell functions including a significant role in generating the vast supply of cellular energy. Indeed, the gradual decline of mitochondrial function is believed to be a hallmark and possible cause of aging. Paradoxically, mild mitochondrial dysfunction early in life extends lifespan in various model organisms. Cells use diverse approaches to promote mitochondrial homeostasis, including the transcriptional reprogramming of cells by mitochondrial unfolded protein response (UPRmt) to mitigate mitochondrial stress. Consistently, UPRmt activation …

Utilizing Β-Gal To Visualize Selective Transport Of The Ssa4 Gene In S.Cerevisiae, Ian M. Staertow, Rebecca L. Adams Phd

Science University Research Symposium (SURS)

In eukaryotic cells such as Saccharomyces cerevisiae, protein synthesis begins with the transport of mRNA from the nucleus to the cytoplasm. In order for mRNA to leave the nucleus, it must first bind to specific transport proteins which can then facilitate transport via the nuclear pore complex (NPC), a selectively permeable membrane within the cell's nuclear envelope. Under environmental stress, such as heat shock, S. cerevisiae cells modulate transport rates. In this case, in heat stress or “heat shock” most mRNA transcripts will remain in the nucleus. The SSA4 transcript encodes for a chaperone protein which facilitates the subsequent export …

Neuroinflammatory Signaling And Immune Cell Infiltration Differ In Brains Of Rats Exposed To Space Radiation And Social Isolation, Austin M. Adkins, Zachary N. M. Luyo, Alea F. Boden, Riley S. Heerbrandt, Richard A. Britten, Laurie L. Wellman, Larry D. Sanford

Center for Integrative Neuroscience and Inflammatory Diseases (CINID) Faculty Publications

Astronauts on the proposed Mars missions will be exposed to extended periods of social isolation (SI) and space radiation (SR). SI and SR-induced immune dysregulation can result in persistent neuroinflammation and neuronal damage which could negatively impact an astronaut’s health and ability to maintain adequate levels of performance. The synergistic effects of combined SI and SR on immune system functionality and the brain remain unknown. Determining how single and combined inflight stressors modulate the immune system is crucial for fully understanding pathways impacting astronaut health and performance. We used ground-based analogs of SI and SR in rodent models to investigate …

Derivation Of The Maintenance Energy Requirements In Growing Jersey Heifers: Supplementary Table S1, Addison L. Carroll, Michael J. Vandehaar, Paul J. Kononoff

Department of Animal Science: Faculty Publications

Supplemental table for Addison L. Carroll, Michael J. VandeHaar, and Paul J. Kononoff. Derivation of the maintenance energy requirements in growing Jersey heifers. Journal of Dairy Science (2025).

Beyond Homogeneity: Exploring Causal Heterogeneity In Psychopathology, Philip B. Vinh

Theses and Dissertations

Traditional models in psychiatric research often impose assumptions of causal homogeneity, treating population-level associations as reflective of uniform underlying mechanisms. This dissertation challenges that assumption by introducing statistical and machine learning frameworks designed to detect and model causal heterogeneity in the development of psychopathology. Central to this approach is the advancement of finite mixture structural equation modeling (FM-SEM) to identify latent subgroups characterized by distinct, and sometimes opposing, causal pathways.

The dissertation comprises three integrated empirical studies. The first introduces mixDoC, a finite mixture extension of the classical Direction of Causation (DoC) model applied to twin data, enabling the detection …

Assessment Of The Genetic Population Structure And Extent Of Clonality In A Rare Serpentine Endemic, Lathyrus Biflorus T.W. Nelson & J.P. Nelson (Fabaceae), Using Ddrad Sequencing, Ashley Dickinson

Cal Poly Humboldt theses and projects

Lathyrus biflorus, or the two-flowered pea, is a rare herbaceous perennial restricted to a single population in Northern California. The species is considered critically imperiled but remains unprotected under state or federal endangered species acts. Despite its rarity, little is known about its life history, reproductive biology, or genetic diversity. Using genome-wide reduced representation sequencing, this study aimed to address these gaps by investigating the molecular evidence of clonality, the number and diversity of genets (unique genetic individuals which can be made up of one or many clonal units or ramets), and overall genetic health of the population. My …

Patterns Of Kinship And Sociality In North American River Otters, Whitney E. Vickers

Cal Poly Humboldt theses and projects

Previous studies of river otters (Lontra canadensis) in coastal Humboldt County, California have documented varying social group compositions over the last four decades. It has been assumed that otters travel between coastal wetland sites, but the extent of movement has been unknown. Socially, river otters have been observed alone, in small family groups that consisted of an otter mom and pup(s), in larger helper groups that consisted of an otter mom, pup(s), and at least one additional adult or juvenile (helpers), and in all-adult social groups. Until now it was unknown whether the composition of social groups was …

Doves And Symbiotic Bacteria: Whole-Genome Assembly And Phylogenomic Inference, Mariam Topchyan

Theses and Dissertations

Part 1

I examined a potential source of variation in phylogenetic inference, investigating whether handling single-nucleotide polymorphisms (SNPs) through different methods during reference-guided genome assembly of pigeon and dove species impacts phylogenetic reconstruction and inference. Specifically, I created a custom consensus base calling tool that handles allelic variation through two different approaches, either ignoring heterozygous sites by denoting them as an ambiguous character “N,” or using a pseudo-random choice between supported base variants. Through reference-guided assembly of 108 dove species, I generated two datasets of alignments using both consensus calling methods, created two trees from both datasets via supermatrix and …

History, Annotated Gazetteer, And Bibliography Of Ornithology In Kalimantan, Indonesian Borneo, Frederick H. Sheldon, Mohammad Irham, Daisy G. S. Kho, Erik Meijaard, Subir B. Shakya, Dewi M. Prawiradilaga, Sebastianus (Bas) Van Balen

Occasional Papers of the Museum of Natural Science, Louisiana State University

Kalimantan comprises nearly three quarters of the island of Borneo and is the place where scientific study of Bornean birds began. We describe the history of bird research in Kalimantan from its beginning, highlighting the ornithologists who explored the region and how their interests and methods changed over time, from a concentration on specimen collection, to examinations of community ecology, to conservation in the face of habitat change and species depletion, to the latest investigations using satellite, genetic, and digital technology. We also highlight some future directions for research, especially the need for more work on basic ecology and biogeography. …

Potential Of Using Trembling Aspen To Make Structural Engineered Wood Products, Dawei Wang

Aspen Bibliography

Trembling aspen (Populus tremuloides) is abundant in Canada but is widely considered an underutilized species. This study was aimed at evaluating the potential of using aspen lumber to produce cross-laminated timber (CLT), glued-laminated timber (glulam), and wood I-joists. The key mechanical properties of these engineered wood products, which were fabricated using a modified grading criterion, were examined. It was found that 1) The mean effective bending stiffness and characteristic bending moment resistance of 5-layer CLT specimens in the major-strength direction were 5,069x10⁹ N·mm²/m and 97.65x10⁶ N·mm/m; 2) The mean apparent MOE and characteristic modulus …

Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …

Periconceptual Nutrition And The Preimplantation Embryo: Approaches For Intervention And Generational Health, Abigail Klein

Dissertations and Theses

The typical American diet exceeds dietary fat recommendations, contributing to the rising rates of obesity. This negatively impacts fertility, pregnancy and fetal growth, and lifelong offspring health. During pregnancy, this also increases risk of co-morbidities like gestational diabetes. Despite this, lipids are not screened during pregnancy and limited research exists evaluating these co-exposures on offspring health. Our lab used a rat model of maternal high fat (HF) diet with late-gestation diabetes (DM) to demonstrate that mitochondrial dysfunction and oxidative stress incite lifelong cardiometabolic disease risk in offspring. To determine the timing of damage, we hypothesized that maternal overnutrition incites mitochondrial …

Using Rna Sequencing To Examine Encephalic Gene Expression In Cactus Mice, Sarah A. Nicholls

Honors Theses and Capstones

Many of the exact mechanisms by which desert-adapted animals avoid dehydration-induced complications are unknown, though there are likely ties to the general mammalian dehydration response, a multisystem process spearheaded by the brain. Peromyscus eremicus, the cactus mouse, can survive its whole life without intaking water and is commonly used as a model to study desert adaptations. In this study, we have used bulk transcriptomics to characterize the differential gene expression across hydrated and dehydrated P. eremicus in five major regions of the brain: the cerebral cortex (referred to throughout much of this paper as the cortex), hippocampus, thalamus, midbrain, …